Author(s)

Nobuhiro Uwa¹, Hiroyuki Hao², Yoshitane Tsukamoto², Tomonori Terada¹, Kosuke Sagawa¹, Takeshi Mohri¹, Takashi Daimon³, Hiroshi Doi⁴, Yohei Sotsuka⁵, Guillaume van Eys⁶, Marie-Luce Bochaton-Piallat⁷, Seiichi Hirota², Masafumi Sakagami¹

¹Department of Otolaryngology, Hyogo College of Medicine, Nishinomiya, Japan.
²Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan.
³Department of Biostatistics, Hyogo College of Medicine, Nishinomiya, Japan.
⁴Department of Radiology, Hyogo College of Medicine, Nishinomiya, Japan.
⁵Department of Plastic Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
⁶Department of Genetics and Cell Biology, University of Maastricht, Maastricht, The Netherlands.
⁷Department of Pathology and Immunology, University of Geneva-CMU, Geneva, Switzerland.

Objective: To evaluate the incidence of cervical angiopathy caused by radiation therapy for head and neck cancer. Methods: Segments of 57 cervical arteries were obtained during surgery for head and neck malignant tumors and divided into two groups (irradiated group and non-irradiated group) based on the treatment prior to vascular resection. In order to evaluate vascular injury after radiation therapy, we examined the degree of medial atrophy, medial fibrosis, smooth muscle cell (SMC) differentiation in the media and intima, intimal hyperplasia and endothelial cell (EC) injury. Sections of arterial segments were stained with hematoxylin-eosin, Elastica van Gieson and Masson’s trichrome, and immunohistochemistry for α-smooth muscle actin (α-SMA), smoothelin, S100A4 and CD31 in the resected vessels was conducted. Results: The median interval between the completion of radiation therapy and vascular resection was nine months. No significant differences were observed between the two groups in terms of medial atrophy, medial fibrosis and intimal hyperplasia. The ratio of the smoothelin-positive area per α-SMA-positive area in the media and the S100A4-positive proportion in the intima, indicating the degree of differentiation of the medial SMC and dedifferentiation of the intimal SMC, respectively, showed no significant differences, despite the tendency toward a lower smoothelin-positive area per α-SMA-positive area in the media of the irradiated arteries. The EC coverage revealed on CD31 immunohistochemistry was significantly decreased, with mural thrombus adhesion, in the irradiated group. Conclusions: The ECs of small arteries are damaged by irradiation. Although we did not confirm the statistical significance of medial SMC dedifferentiation, a decreased expression of smoothelin tended to be observed in the media of the irradiated arteries. Our findings provide histopathological evidence of irradiation angiopathy in head and neck cancer and may help to improve the surgical safety of microvascular anastomosis and determine the treatment strategy for head and neck tumors.

Angiopathy, Endothlial Cell, Pathology, Radiation, Head and Neck

Uwa, N. , Hao, H. , Tsukamoto, Y. , Terada, T. , Sagawa, K. , Mohri, T. , Daimon, T. , Doi, H. , Sotsuka, Y. , Eys, G. , Bochaton-Piallat, M. , Hirota, S. and Sakagami, M. (2015) Histopathological Evidence for Irradiation Angiopathy in Head and Neck Cancer. International Journal of Otolaryngology and Head & Neck Surgery, 4, 108-114. doi: 10.4236/ijohns.2015.42020.